http://www.medicinenet.com/systemic_lupus/page2.

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Medical Author:
William C. Shiel Jr., MD, FACP, FACR
Medical Editor:
Melissa Conrad Stppler, MD

What is lupus? What are the types of lupus?

Lupus is an autoimmune disease characterized by acute and chronic inflammation of various
tissues of the body. Autoimmune diseases are illnesses that occur when the body's tissues are
attacked by its own immune system. The immune system is a complex system within the
body that is designed to fight infectious agents, such as bacteria and other foreign microbes.
One of the ways that the immune system fights infections is by producing antibodies that
bind to the microbes. People with lupus produce abnormal antibodies in their blood that
target tissues within their own body rather than foreign infectious agents. Because the
antibodies and accompanying cells of inflammation can affect tissues anywhere in the body,
lupus has the potential to affect a variety of areas. Sometimes lupus can cause disease of the
skin, heart, lungs, kidneys, joints, and/or nervous system. When only the skin is involved, the
condition is called lupus dermatitis or cutaneous lupus erythematosus. A form of lupus
dermatitis that can be isolated to the skin, without internal disease, is called discoid lupus.
When internal organs are involved, the condition is referred to as systemic lupus
erythematosus (SLE).
Both discoid and systemic lupus are more common in women than men (about eight times
more common). The disease can affect all ages but most commonly begins from 20-45 years
of age. Statistics demonstrate that lupus is somewhat more frequent in African Americans and
people of Chinese and Japanese descent.
What causes lupus? Is lupus hereditary?

The precise reason for the abnormal autoimmunity that causes lupus is not known. Inherited
genes, viruses, ultraviolet light, and certain medications may all play some role.
Genetic factors increase the tendency of developing autoimmune diseases, and autoimmune
diseases such as lupus, rheumatoid arthritis, and autoimmune thyroid disorders are more
common among relatives of people with lupus than the general population. Some scientists
believe that the immune system in lupus is more easily stimulated by external factors like
viruses or ultraviolet light. Sometimes, symptoms of lupus can be precipitated or aggravated
by only a brief period of sun exposure.
It also is known that some women with SLE can experience worsening of their symptoms
prior to their menstrual periods. This phenomenon, together with the female predominance of
SLE, suggests that female hormones play an important role in the expression of SLE. This
hormonal relationship is an active area of ongoing study by scientists.
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More recently, research has demonstrated evidence that a key enzyme's failure to dispose of
dying cells may contribute the development of SLE. The enzyme, DNase1, normally
eliminates what is called "garbage DNA" and other cellular debris by chopping them into tiny
fragments for easier disposal. Researchers turned off the DNase1 gene in mice. The mice
appeared healthy at birth, but after six to eight months, the majority of mice without DNase1
showed signs of SLE. Thus, a genetic mutation in a gene that could disrupt the body's cellular
waste disposal may be involved in the initiation of SLE.

What is drug-induced lupus?

Dozens of medications have been reported to trigger SLE. However, more than 90% of cases
of "drug-induced lupus" occurs as a side effect of one of the following six drugs: hydralazine
(Apresoline is used for high blood pressure); quinidine (Quinidine Gluconate, Quinidine
Sulfate) and procainamide (Pronestyl; Procan-SR; Procanbid) are used for abnormal heart
rhythms; phenytoin (Dilantin) is used for epilepsy; isoniazid ([Nydrazid, Laniazid] used for
tuberculosis); and d-penicillamine (used for rheumatoid arthritis). These drugs are known to
stimulate the immune system and cause SLE. Fortunately, drug-induced SLE is infrequent
(accounting for less than 5% of all people with SLE) and usually resolves when the
medications are discontinued.

What are lupus symptoms and signs?

People with SLE can develop different combinations of symptoms and organ involvement.
Common complaints and symptoms include fatigue, low-grade fever, loss of appetite, muscle
aches, arthritis, ulcers of the mouth and nose, facial rash ("butterfly rash"), unusual sensitivity
to sunlight (photosensitivity), inflammation of the lining that surrounds the lungs (pleuritis)
and the heart (pericarditis), and poor circulation to the fingers and toes with cold exposure
(Raynaud's phenomenon). Complications of organ involvement can lead to further symptoms
that depend on the organ affected and severity of the disease.
Skin manifestations are frequent in lupus and can sometimes lead to scarring. In discoid
lupus, only the skin is typically involved. The skin rash in discoid lupus often is found on the
face and scalp. It usually is red and may have raised borders. Discoid lupus rashes are usually
painless and do not itch, but scarring can cause permanent hair loss (alopecia). Over time,
5%-10% of those with discoid lupus may develop SLE.
Over half of the people with SLE develop a characteristic red, flat facial rash over the bridge
of their nose. Because of its shape, it is frequently referred to as the "butterfly rash" of SLE.
The rash is painless and does not itch. The facial rash, along with inflammation in other
organs, can be precipitated or worsened by exposure to sunlight, a condition called
photosensitivity. This photosensitivity can be accompanied by worsening of inflammation
throughout the body, called a "flare" of the disease.

Picture of a butterfly rash on the face, a characteristic sign of

systemic lupus erythematosus (SLE)
Typically, with treatment, this rash can heal without permanent scarring.
Most people with SLE will develop arthritis during the course of their illness. Arthritis in
SLE commonly involves swelling, pain, stiffness, and even deformity of the small joints of
the hands, wrists, and feet. Sometimes, the arthritis of SLE can mimic that of rheumatoid
arthritis (another autoimmune disease).
More serious organ involvement with inflammation occurs in the brain, liver, and kidneys.
White blood cells and blood-clotting factors also can be characteristically decreased in SLE,
known as leukopenia (leucopenia) and thrombocytopenia, respectively. Leukopenia can
increase the risk of infection, and thrombocytopenia can increase the risk of bleeding.
Inflammation of muscles (myositis) can cause muscle pain and weakness. This can lead to
elevations of muscle enzyme levels in the blood.
Inflammation of blood vessels (vasculitis) that supply oxygen to tissues can cause isolated
injury to a nerve, the skin, or an internal organ. The blood vessels are composed of arteries
that pass oxygen-rich blood to the tissues of the body and veins that return oxygen-depleted
blood from the tissues to the lungs. Vasculitis is characterized by inflammation with damage
to the walls of various blood vessels. The damage blocks the circulation of blood through the
vessels and can cause injury to the tissues that are supplied with oxygen by these vessels.
Inflammation of the lining of the lungs (pleuritis) and of the heart (pericarditis) can cause
sharp chest pain. The chest pain is aggravated by coughing, deep breathing, and certain
changes in body position. The heart muscle itself rarely can become inflamed (carditis). It has
also been shown that young women with SLE have a significantly increased risk of heart
attacks due to coronary artery disease.

Kidney inflammation in SLE can cause leakage of protein into the urine, fluid retention, high
blood pressure, and even kidney failure. This can lead to further fatigue and swelling of the
legs and feet. With kidney failure, machines are needed to cleanse the blood of accumulated
waste products in a process called dialysis.
Involvement of the brain can cause personality changes, thought disorders (psychosis),
seizures, and even coma. Damage to nerves can cause numbness, tingling, and weakness of
the involved body parts or extremities. Brain involvement is referred to as lupus cerebritis.
Many people with SLE experience hair loss (alopecia). Often, this occurs simultaneously
with an increase in the activity of their disease. The hair loss can be patchy or diffuse and
appear to be more like hair thinning.
Some people with SLE have Raynaud's phenomenon. In this condition, the blood supply to
the fingers and/or toes becomes compromised upon exposure to cold, causing blanching,
whitish and/or bluish discoloration, and pain and numbness in the exposed fingers and toes.
Other conditions that can accompany lupus include fibromyalgia, coronary heart disease,
nonbacterial valvular heart disease, pancreatitis, esophagus disease with difficulty swallowing
(dysphagia), liver disease (lupoid hepatitis), and infections.

How is lupus diagnosed?

Since individuals with SLE can have a wide variety of symptoms and different combinations
of organ involvement, no single test establishes the diagnosis of systemic lupus. To help
doctors improve the accuracy of the diagnosis of SLE, 11 criteria were established by the
American Rheumatism Association. These 11 criteria are closely related to the symptoms
discussed above. Some people suspected of having SLE may never develop enough criteria
for a definite diagnosis. Other people accumulate enough criteria only after months or years
of observation. When a person has four or more of these criteria, the diagnosis of SLE is
strongly suggested. Nevertheless, the diagnosis of SLE may be made in some settings in
people with only a few of these classical criteria, and treatment may sometimes be instituted
at this stage. Of these people with minimal criteria, some may later develop other criteria, but
many never do.
The 11 criteria used for diagnosing systemic lupus erythematosus are

malar (over the cheeks of the face) "butterfly" rash,

discoid skin rash (patchy redness with hyperpigmentation and hypopigmentation that
can cause scarring),

photosensitivity (skin rash in reaction to sunlight [ultraviolet light] exposure),

mucous membrane ulcers (spontaneous ulcers of the lining of the mouth, nose, or
throat),

arthritis (two or more swollen, tender joints of the extremities),

pleuritis or pericarditis (inflammation of the lining tissue around the heart or lungs,
usually associated with chest pain upon breathing or changes of body position),

kidney abnormalities (abnormal amounts of urine protein or clumps of cellular

elements called casts detectable with a urinalysis),

brain irritation (manifested by seizures [convulsions] and/or psychosis),

blood-count abnormalities (low counts of white or red blood cells, or platelets, on

routine blood testing),

immunologic disorder (abnormal immune tests include anti-DNA or anti-Sm [Smith]

antibodies, falsely positive blood test for syphilis, anticardiolipin antibodies, lupus
anticoagulant, or positive LE prep test),

and antinuclear antibody (positive ANA antibody testing [antinuclear antibodies in the
blood]).

In addition to the 11 criteria, other tests can be helpful in evaluating people with SLE to
determine the severity of organ involvement. These include routine testing of the blood to
detect inflammation (for example, tests called the sedimentation rate and C-reactive protein),
blood-chemistry testing, direct analysis of internal body fluids, and tissue biopsies.
Abnormalities in body fluids and tissue samples (kidney, skin, and nerve biopsies) can further
support the diagnosis of SLE. The appropriate testing procedures are selected for the patient
individually by the doctor.
What is the treatment for systemic lupus erythematosus?

There is no permanent cure for SLE. The goal of treatment is to relieve symptoms and protect
organs by decreasing inflammation and/or the level of autoimmune activity in the body. The
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precise treatment is decided on an individual basis. Many people with mild symptoms may
need no treatment or only intermittent courses of anti-inflammatory medications. Those with
more serious illness involving damage to internal organ(s) may require high doses of
corticosteroids in combination with other medications that suppress the body's immune
system.
People with SLE need more rest during periods of active disease. Researchers have reported
that poor sleep quality was a significant factor in developing fatigue in people with SLE.
These reports emphasize the importance for people and physicians to address sleep quality
and the effect of underlying depression, lack of exercise, and self-care coping strategies on
overall health. During these periods, carefully prescribed exercise is still important to
maintain muscle tone and range of motion in the joints.
Nonsteroidal anti-inflammatory drugs (NSAIDs) are helpful in reducing inflammation and
pain in muscles, joints, and other tissues. Examples of NSAIDs include aspirin, ibuprofen
(Motrin), naproxen (Naprosyn), and sulindac (Clinoril). Since the individual response to
NSAIDs varies, it is common for a doctor to try different NSAIDs to find the most effective
one with the fewest side effects. The most common side effects are stomach upset, abdominal
pain, ulcers, and even ulcer bleeding. NSAIDs are usually taken with food to reduce side
effects. Sometimes, medications that prevent ulcers while taking NSAIDs, such as
misoprostol (Cytotec), are given simultaneously.
Corticosteroids are more potent than NSAIDs in reducing inflammation and restoring
function when the disease is active. Corticosteroids are particularly helpful when internal
organs are affected. Corticosteroids can be given by mouth, injected directly into the joints
and other tissues, or administered intravenously. Unfortunately, corticosteroids have serious
side effects when given in high doses over prolonged periods, and the doctor will try to
monitor the activity of the disease in order to use the lowest doses that are safe. Side effects
of corticosteroids include weight gain, thinning of the bones and skin, infection, diabetes,
facial puffiness, cataracts, and death (necrosis) of the tissues in large joints.
Hydroxychloroquine (Plaquenil) is an antimalarial medication found to be particularly
effective for SLE people with fatigue, skin involvement, and joint disease. Consistently
taking Plaquenil can prevent flare-ups of lupus. Side effects are uncommon but include
diarrhea, upset stomach, and eye-pigment changes. Eye-pigment changes are rare but require
monitoring by an ophthalmologist (eye specialist) during treatment with Plaquenil.
Researchers have found that Plaquenil significantly decreased the frequency of abnormal
blood clots in people with systemic lupus. Moreover, the effect seemed independent of
immune suppression, implying that Plaquenil can directly act to prevent the blood clots. This
fascinating study highlights an important reason for people and doctors to consider Plaquenil
for long-term use, especially for those SLE people who are at some risk for blood clots in
veins and arteries, such as those with phospholipid antibodies (cardiolipin antibodies, lupus
anticoagulant, and false-positive venereal disease research laboratory test). This means not
only that Plaquenil reduces the chance for re-flares of SLE, but it can also be beneficial in
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thinning the blood to prevent abnormal excessive blood clotting. Plaquenil is commonly used
in combination with other treatments for lupus.
For resistant skin disease, other antimalarial drugs, such as chloroquine (Aralen) or
quinacrine, are considered and can be used in combination with hydroxychloroquine.
Alternative medications for skin disease include dapsone and retinoic acid (Retin-A). Retin-A
is often effective for an uncommon wart-like form of lupus skin disease. For more severe skin
disease, immunosuppressive medications are considered as described below.
Medications that suppress immunity (immunosuppressive medications) are also called
cytotoxic drugs. Immunosuppressive medications are used for treating people with more
severe manifestations of SLE, such as damage to internal organ(s). Examples of
immunosuppressive medications include methotrexate (Rheumatrex, Trexall), azathioprine
(Imuran), cyclophosphamide (Cytoxan), chlorambucil (Leukeran), and cyclosporine
(Sandimmune). All immunosuppressive medications can seriously depress blood-cell counts
and increase risks of infection and bleeding. Immunosuppressive medications may not be
taken during pregnancy or conception because of risk to the fetus. Other side effects are
specific for each drug. For examples, Rheumatrex can cause liver toxicity, while
Sandimmune can impair kidney function.
In recent years, mycophenolate mofetil (CellCept) has been used as an effective medication
for lupus, particularly when it is associated with kidney disease. CellCept has been helpful in
reversing active lupus kidney disease (lupus renal disease) and in maintaining remission after
it is established. Its lower side-effect profile has advantage over traditional immunesuppression medications.
In SLE patients with serious brain or kidney disease, plasmapheresis (a process of removing
and treating the blood before it is returned to the body) is sometimes used to remove
antibodies and other immune substances from the blood to suppress immunity. Rarely, people
with SLE can develop seriously low platelet levels, thereby increasing the risk of excessive
and spontaneous bleeding. Since the spleen is believed to be the major site of platelet
destruction, surgical removal of the spleen is sometimes performed to improve platelet levels.
Other treatments have included plasmapheresis and the use of male hormones.
Plasmapheresis has also been used to remove proteins (cryoglobulins) that can lead to
vasculitis. End-stage kidney damage from SLE requires dialysis and/or a kidney transplant.
Most recent research is indicating benefits of rituximab (Rituxan) in treating lupus.
Rituximab is an intravenously infused antibody that suppresses a particular white blood cell,
the B cell, by decreasing their number in the circulation. B cells have been found to play a
central role in lupus activity, and when they are suppressed, the disease tends toward
remission. This may particularly helpful for people with kidney disease.
Another new B-cell-suppressing treatment is belimumab (Benlysta). Belimumab blocks the
stimulation of the B cells (a B-lymphocyte stimulator or BLyS-specific inhibitor) and is
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indicated for the treatment of adult patients with active, autoantibody-positive systemic lupus
erythematosus who are receiving standard therapy. It is important to note that the efficacy of
belimumab has not been evaluated in patients with severe active lupus nephritis or severe
active central nervous system lupus. Belimumab has not been studied in combination with
other biologic therapies or intravenous cyclophosphamide.
Scientists have also found that low-dose dietary supplementation with omega-3 fish oils
could help patients with lupus by decreasing disease activity and possibly decreasing heartdisease risk.

How can a lupus patient help prevent disease activity (flares)?

SLE is undoubtedly a potentially serious illness with involvement of numerous organ

systems. However, it is important to recognize that most people with SLE lead full, active,
and healthy lives. Periodic increases in disease activity (flares) can usually be managed by
varying medications. Since ultraviolet light can precipitate and worsen flares, people with
systemic lupus should avoid sun exposure. Sunscreens and clothing covering the extremities
can be helpful. Abruptly stopping medications, especially corticosteroids, can also cause
flares and should be avoided. People with SLE are at increased risk of infections, especially if
they are taking corticosteroids or immunosuppressive medications. Therefore, any
unexpected fever should be reported and evaluated.
The key to successful management of SLE is regular contact and communication with the
doctor, allowing monitoring of symptoms, disease activities, and treatment of side effects.
How can systemic lupus erythematosus affect pregnancy or the newborn?

Women with SLE who become pregnant are considered "high risk." Women with SLE who
are pregnant require close observation during pregnancy, delivery, and the postpartum period.
This includes fetal monitoring by the obstetrician during later pregnancy. These women can
have an increased risk of miscarriages (spontaneous abortions) and can have flares of SLE
during pregnancy. The presence of phospholipid antibodies, such as cardiolipin antibodies or
lupus anticoagulant, in the blood can identify people at risk for miscarriages. Cardiolipin
antibodies are associated with a tendency toward blood clotting. People with SLE who have
cardiolipin antibodies or lupus anticoagulant may need blood-thinning medications (aspirin
with or without heparin) during pregnancy to prevent miscarriages. Other reported treatments
include the use of intravenous gamma globulin for selected people with histories of
premature miscarriage and those with low blood-clotting elements (platelets) during
pregnancy. Pregnant women who have had a previous blood-clotting event may benefit by
continuation of blood-thinning medications throughout and after pregnancy for up to six to 12
weeks, at which time the risk of clotting associated with pregnancy seems to diminish.
Plaquenil has now been found to be safe for use to treat SLE during pregnancy.

Lupus antibodies can be transferred from the mother to the fetus and result in lupus illness in
the newborn ("neonatal lupus"). This includes the development of low red cell (anemia)
and/or white blood cell and platelet counts and skin rash. Problems can also develop in the
electrical system of the baby's heart (congenital heart block). Occasionally, a pacemaker for
the baby's heart is needed in this setting. Neonatal lupus and congenital heart block are more
common in newborns of mothers with SLE who carry antibodies referred to as anti-Ro (or
SS-A) and anti-La (or SS-B). (It is wise for the newborn baby's doctor to be made aware if
the mother is known to carry these antibodies, even prior to delivery. The risk of heart block
is 2%; the risk of neonatal lupus is 5%.) Neonatal lupus usually clears after 6 months of age,
as the mother's antibodies are slowly metabolized by the baby.
What does the future hold for people with lupus?

Overall, the outlook for people with systemic lupus is improving each decade with the
development of more accurate monitoring tests and treatments.
The role of the immune system in causing diseases is becoming better understood through
research. This knowledge will be applied to design safer and more effective treatment
methods. For example, completely revising the immune system of people with extremely
aggressive treatments that virtually temporarily wipe out the immune system is being
evaluated. Current studies involve immune eradication with or without replacement of cells
that can re-establish the immune system (stem cell transplantation).
It should be noted that people with SLE are at a somewhat increased risk for developing
cancer. The cancer risk is most dramatic for blood cancers, such as leukemia and lymphoma,
but is also increased for breast cancer. This risk probably relates, in part, to the altered
immune system that is characteristic of SLE.
Women with SLE appear to be at increased risk for heart disease (coronary artery disease)
according to recent reports. Women with SLE should be evaluated and counseled to minimize
risk factors for heart disease, such as elevated blood cholesterol, quitting smoking, high blood
pressure, and obesity.
DHEA (dehydroepiandrosterone) has been helpful in reducing fatigue, improving thinking
difficulties, and improving quality of life in people with SLE. Recent research indicates that
DHEA has been shown to improve or stabilize signs and symptoms of SLE. DHEA is
commonly available in health-food stores, pharmacies, and many groceries.
Landmark research has shown clearly that oral contraceptives do not increase the rate of
flares of systemic lupus erythematosus. This important finding is opposite to what has been
thought for years. Now we can reassure women with lupus that if they take birth-control pills,
they are not increasing their risk for lupus flares. NOTE: Birth-control pills or any estrogen
medications should still be avoided by women who are at increased risk of blood clotting,
such as women with lupus who have phospholipid antibodies (including cardiolipin antibody
and lupus anticoagulant).
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Individuals with SLE can improve their prognosis by learning about the many aspects of the
illness as well as closely monitoring their own health with their doctors.

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